Morgan E. Grams, MD, MHS, is an Assistant Professor in the Division of Nephrology at Johns Hopkins University. She seeks a Mentored Patient-Oriented Research Career Development Award in order to obtain essential skills and mentored research experience for an independent career as a physician scientist in the field of chronic kidney disease. The research proposal details a five-year plan consisting of doctoral-level coursework in Clinical Epidemiology, mentorship by Dr. Josef Coresh, MD, PhD, and Dr. Dorry L. Segev, MD, PhD, and epidemiologic research in the cardiovascular and mortality risks associated with chronic kidney disease. The specific aims of the research agenda are to: 1) Characterize cardiovascular and mortality risk among individuals with advanced chronic kidney disease; 2) Identify risk factors for death and cardiovascular endpoints in preemptively listed transplant candidates before and after the initiation of renal replacement therapy; and 3) Estimate the optimal level of native kidney function at which a viable transplant candidate should be transplanted. Immediate career goals include the mastery of advanced meta-analysis techniques, methods of causal inference, and Markov decision process models through an academic curriculum integrated with the research plan. Long-term, Dr. Grams aims to lead independent research programs investigating optimal treatment and decision-making in advanced chronic kidney disease. Completion of the proposed aims will provide vital information relevant to the one million U.S. patients with pre-dialysis stage 4-5 chronic kidney disease. Chronic kidney disease is associated with exceedingly high rates of cardiovascular morbidity and mortality, but the optimal treatment of this population remains unknown. Preemptive kidney transplantation, or transplantation prior to the initiation of maintenance dialysis, is an increasingly common therapy. Similar to trends in dialysis initiation, it is being performed earlie in the course of chronic kidney disease progression. A better understanding of the optimal timing of kidney transplantation may inform national policies governing deceased donor kidney listing and allocation, and also improve clinical decision-making for pre-dialysis transplant patients with living donors. Furthermore, identification of characteristics associated with high cardiovascular and mortality risk may be used to guide therapy and future trials in the advanced chronic kidney disease population. PUBLIC HEALTH RELEVANCE: The results of this project will provide evidence-based guidelines for when and in which patients preemptive kidney transplantation should be performed. Moreover, the detailed analysis of outcomes in patients with advanced chronic kidney disease will help inform counseling, treatment and referral practices among this growing population.